Phenotypic and Genetic Characteristics of Retinal Vascular Parameters and their Association with Diseases

Abstract Fundus images allow for non-invasive assessment of the retinal vasculature whose features provide important information on health. Using a fully automated image processing pipeline, we extracted 17 different morphological vascular phenotypes, including median vessels diameter, diameter variability, main temporal angles, vascular density, central retinal equivalents, the number of bifurcations, and tortuosity, from over 130k fundus images of close to 72k UK Biobank subjects. We performed genome-wide association studies (GWAS) of these phenotypes. From this, we estimated their individual heritabilities, ranging between 5 and 25%, and genetic cross-phenotype correlations, which mostly mirrored the corresponding phenotypic correlations, but tended to be slightly larger. Projecting our genetic association signals onto genes and pathways revealed remarkably low overlap suggesting largely decoupled mechanisms modulating the different phenotypes. Our disease phenotype associations confirmed some previously known findings and revealed many novel connections. Notably, diameter variability, especially for the veins, seems to have new and interesting associations with diseases, including heart attack, pulmonary embolism, and age of death. Mendelian Randomization analysis suggests causal influence of blood pressure and body mass index on retinal vessel morphology, among other results. Our analyses provide evidence that large-scale analysis of image-derived vascular phenotypes has sufficient power for obtaining functional, as well as some initial causal insights into the processes modulating the retinal vasculature.